biostudies-literatureEvrony GDNational Institute of Neurological Disorders and StrokeHoward Hughes Medical InstituteLouis Lange III Scholarship in Translational ResearchBoston Children's HospitalNINDS NIH HHSNational Institutes of HealthWilliam Randolph Hearst FundEleanor and Miles Shore FellowshipPaul G. Allen Family FoundationNIGMS NIH HHSe12966https://www.ebi.ac.uk/biostudies/studies/S-EPMC4805530biostudies-literatureUnknown5Whether somatic mutations contribute functional diversity to brain cells is a long-standing question. Single-neuron genomics enables direct measurement of somatic mutation rates in human brain and promises to answer this question. A recent study (Upton et al., 2015) reported high rates of somatic LINE-1 element (L1) retrotransposition in the hippocampus and cerebral cortex that would have major implications for normal brain function, and suggested that these events preferentially impact genes important for neuronal function. We identify aspects of the single-cell sequencing approach, bioinformatic analysis, and validation methods that led to thousands of artifacts being interpreted as somatic mutation events. Our reanalysis supports a mutation frequency of approximately 0.2 events per celleLifeResolving rates of mutation in the brain using single-neuron genomics.PMC4805530R01 NS079277T32GM007753R01 NS079277 and R01 NS032457T32 GM007753R01 NS032457Park PJWalsh CAEvrony GDLee EfalseResolving rates of mutation in the brain using single-neuron genomics.Whether somatic mutations contribute functional diversity to brain cells is a long-standing question. Single-neuron genomics enables direct measurement of somatic mutation rates in human brain and promises to answer this question. A recent study (Upton et al., 2015) reported high rates of somatic LINE-1 element (L1) retrotransposition in the hippocampus and cerebral cortex that would have major implications for normal brain function, and suggested that these events preferentially impact genes important for neuronal function. We identify aspects of the single-cell sequencing approach, bioinformatic analysis, and validation methods that led to thousands of artifacts being interpreted as somatic mutation events. Our reanalysis supports a mutation frequency of approximately 0.2 events per cell2016-01-01T00:00:00Z2016 Feb2026-04-07T14:09:32.025Z2019-03-27T03:10:10ZS-EPMC48055302690144010.7554/eLife.12966